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- Title
Bimodal effects of MK-801 on locomotion and stereotypy in C57BL/6 mice.
- Authors
Jinhua Wu; Hong Zou; Strong, Judith A.; Yu, Jun; Xuedong Zhou; Qinglian Xie; Guoping Zhao; Meilei Jin; Lei Yu
- Abstract
Rationale: Systemic injection of the non-competitive NMDA (N-methyl-D-aspartate) receptor antagonist MK-801 (dizocilpine maleate) causes both increased locomotion in rodents and various stereotypic behaviors that are proposed to model certain aspects of schizophrenic symptoms in humans. Objectives: This study presents a comprehensive characterization of the bimodal effects of MK-801 on locomotion and stereotypy in the C57BL/6 mouse strain, a strain commonly used for genetically modified mice. Results: We found that it is important to analyze both locomotion and stereotypy in parallel, as MK-801-induced stereotypy results in abnormal movements that are recorded as locomotion by automated beam detection systems. Furthermore, it is important to analyze the bimodal effects of MK-801 over an extended time span, rather than the commonly used narrower time window, as at higher doses (e.g., above 0.3 mg/kg) the hyperlocomotion phase develops only after the stereotypic phase subsides. We also observed that the apparent dose-response curve is very sensitive to the particular time window chosen for analysis because MK-801 affects both the time course and maximum value of stimulated locomotion. We show that analyzing the absolute peak value of locomotion induced for each animal, rather than group-averaged time courses, provides a measure that is sensitive over a wider range of MK-801 doses. Interestingly, MK-801 even at a very low dose of 0.02 mg/kg suppressed rather than enhanced rearing behavior, differing in this regard from amphetamine. Conclusions: The non-competitive NMDA receptor antagonist MK-801 induces a complex pattern of behavioral modification in mice with respect to both the time course and the dose-response relationship of behavioral changes. The results of this study provide a foundation and frame of reference for the growing interest in studying MK-801-induced behavior in mice.
- Subjects
METHYL aspartate; LABORATORY rodents; LABORATORY mice; ANIMAL locomotion; ANIMAL behavior
- Publication
Psychopharmacology, 2005, Vol 177, Issue 3, p256
- ISSN
0033-3158
- Publication type
Article
- DOI
10.1007/s00213-004-1944-1